Changes of masseter muscle activity following injection of botulinum toxin type A in adult rats.

OBJECTIVES: To investigate changes in masseter muscle function following intramuscular injection of different dose-dependent botulinum toxin type A (BTXA). SETTING AND SAMPLE POPULATION: Department of Orthodontics at Taipei Medical University. Fifty-two, 70-day-old male Wistar rats were randomly divided into four groups. Group I received 7.5 U of BTXA (0.3 ml), Group II received 5.0 U, and Group III received 2.5 U in the right masseter muscle, respectively. Group IV is the control and received no BTXA injection. MATERIALS AND METHODS: A wire electrode device was implanted to record muscle activity. One week after implantation, the rats were fed every 2 h and EMG signals were recorded during the first hour. All signals were recorded for 12 weeks. Thereafter, EMG data were analyzed for statistical calculation and weights of masseter muscles were measured. RESULTS: Masseter muscle activity decreased 99% during the first week after BTXA injection and gradually recovered from the 3rd week on in Groups I-III. By the 12th week, muscle activity recovered to 41% in Groups I and II and 56.26% in Group III. No significant changes of muscle activity were observed in Group IV. CONCLUSION: BTXA induced a reduction in masseter muscle activity and an increased toxin dose resulted in greater depression of muscle activity.

Hepatitis C viral infection and the risk of dementia.

BACKGROUND AND PURPOSE: Hepatitis C virus (HCV) infection may cause cognitive impairment, but no studies have focused specifically on cognitive impairment stemming from HCV. The purpose of this study was to investigate the potential increased risk for dementia in HCV-infected patients. METHODS: A population-based cohort study based on the Taiwan National Health Insurance Research Database was conducted. From all potential participants aged 50 years or more, a total of 58,570 matched (1:1) pairs of HCV-infected patients and non-HCV-infected patients were included. Each subject was individually tracked from 1997 to 2009 to identify incident cases of dementia (onset in 1999 or later). Cox proportional hazards regressions were employed to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between HCV infection and dementia. RESULTS: There were 2989 dementia cases from the HCV-infected cohort during the follow-up period of 533,861.1 person-years; the overall incidence rates of dementia differed from the non-HCV cohort (56.0 vs. 47.7 cases per 10,000 person-years, P < 0.05). The adjusted HR for dementia was 1.36 (95% CI 1.27-1.42) for HCV-infected patients after adjusting for alcohol-related disease, liver cirrhosis, hepatic encephalopathy and hepatocellular carcinoma. CONCLUSIONS: HCV infection may increase the risk for dementia. Further mechanistic research is needed.

Age- and gender-related long-term renal outcome in patients with lupus nephritis.

OBJECTIVE: To investigate age- and gender-related long-term renal outcome in patients with lupus nephritis (LN). METHODS: This is a retrospective, chart review study of patients with LN at Chang Gung Memorial Hospital, Kaohsiung, between January 1986 and June 2004. All had undergone a renal biopsy that showed LN. The end point of outcome was chronic renal insufficiency (CRI), which was defined as 'doubling of baseline serum creatinine lasting for at least 6 months with a value at least 2 mg/dl.' The patients were categorized by age tertiles and gender. A 5-year survival curve was constructed to study the effect of age and gender on the outcome. RESULTS: In total, 121 sets of patient data were evaluated. The study group included 104 women and 17 men. Of the study patients, 26 (21%) developed CRI after 5 years of follow-up. There was no significant difference among age groups in developing CRI (p = 0.23). In terms of gender, men had worse long-term renal outcome (p = 0.004) than women. CONCLUSIONS: The long-term renal outcome of the LN patients did not differ among age groups, but was worse in men.

Differential effects of high MUFA with high or low P/S ratio (polyunsaturated to saturated fatty acids) on improving hepatic lipolytic enzymes and mediating PPARγ related with lipoprotein lipase and hormone-sensitive lipase of white adipose tissue in diet-induced obese hamster.

OBJECTIVES: The aim of this study was to assess the relationship between high monounsaturated fatty acids (MUFAs) with different levels of polyunsaturated-to-saturated fatty acid (P/S) ratios and body fat loss in diet-induced obesity (DIO) models. DESIGN: Male Golden Syrian hamsters were randomly assigned to the control group (n=12) and obesity group (n=24) for 4 weeks of the high-fat DIO period; afterward, six hamsters from each group were killed. The remaining control hamsters were still fed a low-fat diet. For an additional 8 weeks, the remaining obesity hamsters were switched to a low-fat diet and subdivided into three subgroups (n=6/group): the obesity-control (ObC) group, high MUFA with high P/S ratio oil (HMHR) group and olive oil (OO) group. Serum insulin and leptin concentrations were measured, and hepatic fatty acid metabolic enzymes and adipose differentiation markers were determined using enzyme activities analysis, western blot and semiquantification reverse-transcription PCR. RESULTS: No difference was observed in the mean energy intake through all study periods. After the DIO period, the obesity group increased in weight gain and epididymal fat weight compared with the control group. DIO hamsters in the HMLR group had significant reductions in white adipose tissue deposition and plasma leptin levels, suppression in adipose peroxisome proliferator-activated receptor-γ (PPARγ) and lipoprotein lipase (LPL) mRNA expressions and increases in hepatic acyl-CoA oxidase and carnitine palmitoyltransferase-I activities and mRNA levels compared with those in the ObC group. The HMHR group had upregulated phosphorylation of hormone-sensitive lipase (HSL) relative to total HSL protein levels compared with the OO group. However, the OO group had significantly elevated hepatic de novo lipogenesis compared with the HMHR group. CONCLUSIONS: HMHR seemed to be beneficial in depleting white adipose tissue accumulation by decreasing adipose PPARγ and LPL mRNA expressions and mediating phosphorylation of HSL, and by improving hepatic lipolytic enzyme activities and mRNA expressions involved in ß-oxidation in DIO hamsters.

Correlation between kidney and peripheral nerve functions in Type 2 diabetes.

BACKGROUND: Although greater impairments in nerve functions parameters are most likely to occur with a lower kidney function, there is a paucity of information on the relationship between the kidney and peripheral nerve functions parameters in Type 2 diabetes. AIM: To address the impact of peripheral nerve functions in Type 2 diabetes patients in different stages of chronic kidney diseases (CKD). DESIGN: This prospective study enrolled 238 patients with Type 2 diabetes at a tertiary medical center. METHOD: We designed composite amplitude scores of nerve conductions (CAS) as a measure of severity of peripheral neuropathy (PN), and used estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) parameters to stage CKD in Type 2 diabetes patients. The intrapersonal mean, standard deviation and coefficient of variation of eGFR for 238 patients were obtained in the 3 years prior to the study. RESULTS: The patients who had lower eGFR and higher UACR were older, with longer diabetes duration, a greater percentage of retinopathy and PN and higher CAS. Multiple linear regression analysis revealed that diabetes duration and eGFR were independently associated with CAS, and a cut-off value of eGFR in the presence of PN was 65.3 ml/min/1.73 m2. CONCLUSION: We observed a close relationship between the severity of kidney and peripheral nerve function in patients with diabetes. If a patient's eGFR value is below 65.3 ml/min/1.73 m2 or the UACR value is above 98.6 mg/dl, caution is needed with the presence of PN even in diabetic patients who are asymptomatic.

Resistin facilitates breast cancer progression via TLR4-mediated induction of mesenchymal phenotypes and stemness properties.

Growing evidence indicates that resistin-an obesity-related cytokine-is upregulated in breast cancer patients, yet its impact on breast cancer behavior remains to be ascertained. Similarly, Toll-like receptor 4 (TLR4) has been implicated in breast cancer progression, however, its clinically relevant endogenous ligand remains elusive. In this study, we observed that high serum resistin levels in breast cancer patients positively correlated with tumor stage, size and lymph node metastasis. These findings were replicated in animal models of breast cancer tumorigenesis and metastasis. Resistin was found to promote epithelial-mesenchymal transition and stemness in breast cancer cells-mechanisms critical to tumorigenesis and metastasis-through a TLR4/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)/signal transducer and activator of transcription 3 (STAT3) signaling pathway and negated by TLR4-specific antibody and antagonist. These findings provide clear evidence that resistin is a clinically relevant endogenous ligand for TLR4, which promotes tumor progression via TLR4/NF-κB/STAT3 signaling, providing insights into a novel therapeutic target in breast cancer.

Recurrence of depressive disorders after interferon-induced depression.

Interferon alpha (IFN-α)-treated patients commonly develop depression during the therapy period. Although most IFN-α-induced depressive disorders achieve remission after IFN-α therapy, no studies have examined the long-term mood effects of IFN-α treatment. We conducted a 12-year population-based cohort study of hepatitis C virus (HCV)-infected patients who were older than 20 years and had received IFN-α therapy. The sample was obtained from the Taiwan National Health Insurance Research Database. The cohort included patients with and without IFN-α-induced depression, matched randomly by age, sex and depression history, at a ratio of 1:10. The follow-up started after the last administration of IFN-α and was designed to determine the incidence of recurrent depressive disorder after IFN-α therapy. A total of 156 subjects were identified as having IFN-α-induced depression and achieving full remission after IFN-α therapy. The overall incidence of recurrent depressive disorders among patients with and without IFN-α-induced depression was 56.8 (95% confidence interval (CI), 42.4-76.1) and 4.1 (95% CI, 2.9-5.8) cases, respectively, per 100 000 person-years, P<0.001. The adjusted hazard ratios for recurrent depressive disorder were 13.5 (95% CI, 9.9-18.3) in the IFN-α-treated cohort and 22.2 (95% CI, 11.2-44.2) in the matched cohort for IFN-α-induced depression patients after adjusting for age, sex, income, urbanization and comorbid diseases. IFN-α-induced depression was associated with a high risk of recurrent depression. It was not a transient disease and might be considered an episode of depressive disorder. Continuation therapy might be considered, and further research is needed.

Milrinone, a cyclic AMP-phosphodiesterase inhibitor, has differential effects on regional myocardial work and oxygen consumption in experimental left ventricular hypertrophy.

OBJECTIVE: The aim was to test the hypothesis that local myocardial work and O2 consumption would respond differentially to milrinone, a selective cyclic AMP-phosphodiesterase inhibitor, in left ventricular hypertrophy due to differences in myocardial cyclic AMP-phosphodiesterase activity. METHODS: The effect of milrinone on regional segment work and regional O2 consumption was measured in 12 open chest anaesthetised dogs with left ventricular hypertrophy induced by valvular aortic stenosis and in 10 age matched control dogs. Regional myocardial work was calculated as the integrated product of instantaneous force development (miniature transducer) and segment shortening (sonomicrometer). Regional O2 consumption was calculated from coronary blood flow (radiolabelled microspheres) and O2 saturations in small regional vessels (microspectrophotometry). Low Km phosphodiesterase activity was assayed by measuring the hydrolysis of radiolabelled cyclic AMP. RESULTS: Milrinone increased left ventricular dP/dtmax by approximately 60-70% in both control [2808(SEM 314) to 4584(660) mm Hg.s-1] and left ventricular hypertrophy [3279(258) to 5589(470) mm-Hg.s-1]. Regional work increased significantly in control [612(88) to 955(101) g.mm.min-1], while the increase was not significant in left ventricular hypertrophy [859(139) to 974(172) g.mm.min-1]. Regional O2 consumption increased significantly with milrinone in left ventricular hypertrophy [8.1(1.2) to 13.1(2.4) ml O2.min-1.100 g-1], but the increase was not significant in control [6.9(1.2) to 7.4(1.0) ml O2.min-1.100 g-1]. Myocardial stiffness during ejection was increased by milrinone to a significantly greater extent in animals with left ventricular hypertrophy. These effects were not related to differences in cyclic AMP-phosphodiesterase activity between control hearts and hearts with left ventricular hypertrophy [393(45) v 402(36) pmol.mg protein-1.1]. CONCLUSIONS: Differences between the hypertrophied and normal canine myocardium in response to milrinone are either due to altered levels of cyclic AMP production in left ventricular hypertrophy, to effects of milrinone that are unrelated to cyclic AMP-phosphodiesterase inhibition, or to other differences in hypertrophied hearts. The greater stiffness of the myocardium in left ventricular hypertrophy may require a greater energy expenditure to increase the amount of work it performs.

Risperidone in acutely exacerbated schizophrenia: dosing strategies and plasma levels.

BACKGROUND: The optimal risperidone dosing strategy for acute schizophrenia requires elucidation. Furthermore, plasma levels of risperidone and its active metabolite (9-hydroxyrisperidone) at a given dose vary greatly among different individuals. For patients who metabolize risperidone slowly, a medium dose results in excessively high plasma levels, which might be related to adverse events and perhaps poor response. We thus investigated whether dose reduction to diminish adverse reactions associated with ordinary risperidone doses could still yield efficacy for acutely exacerbated schizophrenia. METHOD: Thirty-one newly hospitalized Chinese patients with acute exacerbation of schizophrenia (DSM-IV) entered this prospective, 6-week open trial. Risperidone doses were titrated to 6 mg/day (if tolerable) over 3 days, but were lowered thereafter if side effects appeared. Efficacy and side effect assessments were conducted on days 0, 4, 14, 28, and 42. Endpoint steady-state plasma levels of risperidone and 9-hydroxyrisperidone were analyzed by high performance liquid chromatography with ultraviolet detection. RESULTS: Thirty patients completed the trial. Of them, 17 tolerated the 6-mg target dose well, while the other 13 received lower final doses (mean +/- SD = 3.6 +/- 0.9 mg, p = .0001) for curtailing treatment-emergent side effects. At endpoint, 92.3% of the 13 low-dose individuals responded to treatment (20% or more reduction in the total Positive and Negative Syndrome Scale score), compared with 52.9% of the 17 high-dose subjects (p < .05). No significant between-group differences were revealed in other minor efficacy measures. Of note, endpoint plasma levels of the active moiety (risperidone plus 9-hydroxyrisperidone) were similar between the low- and high-dose groups (40.4 +/- 31.1 ng/mL vs. 49.7 +/- 13.4 ng/mL, NS). CONCLUSION: The results of this preliminary trial suggest that up to 6 mg of risperidone is efficacious in treating patients with acute exacerbation of schizophrenia. Nearly 60% of the patients could tolerate a 6-mg dose. For the other 40%, reducing dosages to 3.6 +/- 0.9 mg for relieving side effects still yielded efficacy. The 2 dose groups were comparable in the endpoint steady-state plasma drug concentrations.

Acute respiratory distress syndrome among trauma patients: trends in ICU mortality, risk factors, complications and resource utilization.

OBJECTIVE: To evaluate trends in mortality and related factors among trauma patients who developed acute respiratory distress syndrome (ARDS). STUDY: Observational study based on data prospectively gathered in computerized trauma registry. SETTING: Trauma intensive care unit (ICU) of 48 beds in level I trauma center. PATIENTS: All trauma patients with ARDS admitted during 1985-87 (486, group 1 [G1]) and 1993-95 (552, group 2[G2]). METHODS: ARDS was defined by American-European Consensus Conference criteria and the need for 48 h or more on mechanical ventilation with FIO2 greater than 0.50 and PEEP of more than 5 cmH2O. Demographics, severity score, injury-admission delay time, first 24-h transfusion and septic and organ system failure complications were independent variables. ICU mortality was the dependent variable. ICU length of stay (LOS) and life support techniques were considered. Respiratory and renal support strategies were different in the two time periods. RESULTS: Mortality decreased over the period (G1: 29.2% vs G2: 21.4%, p < 0.04), in patients aged both over and under 65 years. Multivariate analysis showed mortality was related to age, severity and time period (G1 1.68-fold that in G2) and that the greater G1 mortality was related to more renal failure and hematologic failure/dysfunction. ICU LOS decreased from 31.7+/-26.7 days (G1) to 27.3+/-22 days (G2) (p < 0.003). CONCLUSIONS: Mortality among trauma patients with ARDS declined over the 8 years studied and was associated with less organ failure. This reduction was probably the result of new approaches to mechanical ventilation, renal failure replacement and vasoactive drug therapy.

Traumatic tricuspid regurgitation with cyanosis: diagnosis by transesophageal echocardiography.

This case report demonstrates the utility of transesophageal echocardiography in the rapid diagnosis of cardiac injury from blunt thoracic trauma. Initial transesophageal echocardiography identified a flail tricuspid valve leaflet and regurgitation in a patient with jugular venous distention and hemodynamic instability. Progressive hypoxemia prompted repeat transesophageal echocardiography with contrast enhancement, which revealed opening of the foramen ovale and a right-to-left interatrial shunt. Operative repair of the lesion was lifesaving.

Relationship between cyclic-AMP content, regional myocardial function and O2 consumption in experimental left ventricular hypertrophy: effect of negative inotropes.

The aim of this study was to examine the hypothesis that negative inotropic agents that lower myocyte cyclic-AMP by different means would have similar effects on local myocardial segment work and O2 consumption in control hearts, but that this response would differ in left ventricular hypertrophy (LVH) induced by aortic valve stenosis. Open chest anesthesized LVH and control dogs were studied before and during esmolol (100 micrograms/kg/min) and acetylcholine (100 micrograms/kg/min) infusion. Regional work was calculated as the integrated product of instantaneous force (miniature transducer) and shortening (sonomicrometry) per min. Regional O2 consumption was calculated from blood flow (radioactive microspheres) and O2 saturation of small frozen vessels (microspectrophotometry). Cyclic-AMP level was determined with a competitive binding assay using 3H-cyclic-AMP and was found to be 731 +/- 90 (mean +/- S.D.) pmol/g in control and 711 +/- 163 in LVH. There were similar decreases in cyclic-AMP levels in control hearts with acetylcholine (365 +/- 135) and the beta adrenergic blocker (430 +/- 95). In LVH, esmolol lowered cyclic-AMP (383 +/- 39), but acetylcholine did not (689 +/- 105). In control animals, regional O2 consumption (7.7 +/- 0.6, 5.6 +/- 0.4 and 5.6 +/- 0.5 ml O2/min/100 g, control, acetylcholine, esmolol, respectively) and segment work (878 +/- 82, 546 +/- 80, 627 +/- 66 g*mm/min) fell to similar levels with these agents. Similar decreases were found in LVH with esmolol for O2 consumption (7.1 +/- 1.2, 5.1 +/- 1.0, baseline, esmolol) and segment work (895 +/- 140, 427 +/- 65). Acetylcholine had no significant effect on segment work (800 +/- 201), but did lower regional O2 consumption (4.0 +/- 0.7) in LVH dogs. It is concluded that there is a strong relationship between the level of cyclic-AMP and myocardial function and O2 consumption in control hearts. The action of acetylcholine is altered in LVH leading to an uncoupling between regional cyclic-AMP, function and metabolism.

Measuring plasminogen activator inhibitor activity in plasma by two enzymatic assays.

We compared two methods that measure plasminogen activator inhibitor (PAI) activity in plasma based on the ability of PAI to inhibit tissue plasminogen activator (tPA) or urokinase (uPA) in order to determine which method most accurately measures plasma PAI activity after stressors, like hemorrhage. Plasma PAI activity was significantly elevated after hemorrhage in both assays. Using standard curves derived from rhPAI-1, we found that the tPA-PAI assay was more sensitive than the uPA-PAI assay. However, we measured a 10-fold difference in PAI activity as measured between assays, suggesting that some endogenous plasma constituents (tPA, uPA, plasminogen or plasmin) may interfere with the accurate determination of PAI activity. Increasing the amount of plasma in each assay led to a progressive increase in PAI activity. However, removing either tPA or plasminogen from the tPA-PAI assay unmasked the presence of some endogenous tPA and plasminogen. Furthermore, increasing plasma volume in either assay increases measured plasma tPA, but not uPA. Finally, plasma tPA is elevated after hemorrhage, whereas plasma uPA is not. These results suggest that endogenous tPA and plasminogen may interfere with the measurement of plasma PAI activity in the tPA-PAI assay after hemorrhage or other stresses. The uPA-PAI assay does not have this confounding problem because endogenous uPA does not interfere with the assay, nor does it rise during hemorrhage.

Cognitive trauma care is undervalued: adult splenic injury as a paradigm.

Nonoperative management (NOM) of adult splenic injury is evolving. Economic aspects of NOM have not been examined. We hypothesize that NOM reduces hospital and professional charges. Surgeon, radiologist, and hospital charges and reimbursements, and clinical outcome were obtained for 77 consecutive adult splenic injury patients (> or = 15 years old) over a 3-year period. NOM succeeded in 30 of 31 patients. NOM was associated with lower surgeon fee ($1,148 vs $4,452; P < 0.0001), surgeon reimbursement ($587 vs $2,773; P = 0.0001), and hospital charge ($18,982 vs $48,790; P = 0.001) relative to operative management. Radiologist fee ($1,776 vs $2,285) and reimbursement ($1,069 vs $1,537) were not significantly affected. No significant difference existed between surgeon (primary care provider) and radiologist reimbursement for NOM. ISS poorly correlated with economic variables. We conclude that cost reductions are another potential advantage of NOM. Surgeon reimbursement for the cognitive skills involved in NOM is minimal. Future health finance policy should recognize the cognitive aspects of trauma care.

Masseter muscle fibre changes following reduction of masticatory function.

This study evaluated histological changes in masseter muscle fibres following reduced masticatory function by injection of botulinum toxin type A (BTX). Sixty 30-day-old Long-Evans male rats were randomly separated into four groups (15 per group): group I BTX masseter, 25U/ml (0.04ml each muscle) BTX was injected in bilateral masseter muscle whilst bilateral temporalis muscles received an equal amount of normal saline; group II BTX temporalis, 25U/ml (0.04ml each muscle) BTX was injected in bilateral temporalis muscle whilst bilateral masseter muscle received an equal amount of normal saline; group III BTX temporalis and masseter, bilateral temporalis and masseter were given 25U/ml (0.04ml each muscle) BTX; group IV normal saline (control), bilateral temporalis and masseter were given normal saline (0.04ml each muscle). After 45 days, the rats were killed, the muscles dissected and mean muscle mass recorded. The superficial masseter muscles were immunohistochemically analysed. Fibre sizes in group III were bigger than those in other groups. There was a small percentage of type IIa fibres in group III. Reduction in muscle fibre size and transition of muscle fibre subtypes from type IIa to IIx or IIb fibres may occur due to reduced masticatory function.

The influence of masticatory hypofunction on developing rat craniofacial structure.

The purpose of this study was to use botulinum neurotoxin type A (BoNT/A) selectively to evaluate the influence of localized masticatory atrophy and paresis on craniofacial growth and development. 60 growing rats, 4 weeks old, weighing approximately 120g, were randomly divided according as follows (Long-Evans, N=15 per group): I (Mb+Tns); II (Mns+Tb); III (Mb+Tb); IV (Mns+Tns), where Mb or Tb is the BoNT/A-injected masseter or temporalis muscles (1.0U/muscle, 2.5ml) and Mns or Tns is the saline-injected muscles (2.5ml). After 7 weeks, the mature rats were killed, the muscles dissected and mean muscle mass recorded. Anthropometric cranial, maxillary and mandibular measurements were taken from the dried skulls. Changes in animal weight during the growth period were not statistically significant. The mean masticatory muscle mass was smaller for the BoNT/A-injected muscles of Mb and Tb. Anthropometric measurements of bony structures inserted by masseter and temporalis muscles revealed a significant treatment effect. The measurements showed a facial morphology typical of a dolichofacial profile: short upper face accompanied by a long lower face with an extended mandibular length and ramus height and constricted bicoronoidal and bigonial widths. The results suggest that induction of localized masticatory muscle atrophy with BoNT/A alters craniofacial growth and development.

Sternal fractures in blunt chest trauma: a practical algorithm for management.

A retrospective review of the medical records of blunt trauma patients with sternal fracture admitted to a level 1 trauma center from June 1990 to June 1993 was undertaken to determine the relationship between sternal fractures and clinically significant myocardial injury, and to assess the usefulness of cardiac evaluation and monitoring in these patients. Of 33 patients with sternal fracture, 31 were in motor vehicle crashes and 2 were pedestrians struck. All had Glasgow Coma Scale score = 15. No patient had a severe, life-threatening, associated injury (Abbreviated Injury Score of >3). No electrocardiogram or echocardiogram showed evidence of acute injury or ischemia. No arrhythmias requiring treatment were noted. No CPK-MB fraction was >5%. These results show that sternal fracture is not a marker for clinically significant myocardial injury. The management of sternal fracture patients should be directed toward the treatment of associated injuries.

Regional asynchrony of segmental contraction may explain the "oxygen consumption paradox" in stunned myocardium.

Despite apparently depressed function, stunned myocardium maintains oxygen consumption and has the capacity to increase contractility with inotropic stimulation. We hypothesized that during stunning, O2 demand is maintained because regional segment work is performed, but is asynchronous with global left ventricular contraction, and that inotropic stimulation would restore regional work and synchrony. Thirteen open-chest anesthetized dogs were subjected to three left anterior descending (LAD) coronary artery occlusions (10 min) and reperfusions (15 min) to produce regional myocardial stunning. Segment shortening and force development were measured independently and simultaneously in the LAD (experimental) region and circumflex (control) regions. Regional myocardial work was calculated as the integrated product of instantaneous force and shortening, during two periods: 1) over the entire cardiac cycle (Positive Work), and 2) limited to the systolic portion of the cardiac cycle (Systolic Work). Regional myocardial O2 consumption (MVO2) was calculated from regional blood flow (radiolabeled microspheres) and O2 saturation data (microspectrophotometry). Occlusion of the LAD produced a delay in onset of segment shortening in the ischemic region, but not in regional force development. A time delay of 67-81 ms persisted through the three stages of occlusions and reperfusions. Systolic regional work was depressed to a greater extent (924 +/- 182 to 149 +/- 118 g*mm*min-1) than total positive regional work (1437 +/- 337 to 857 +/- 174 g*mm*min-1). Regional subepicardial MVO2 in the stunned region was not different than in the control region (7.3 +/- 1.5 vs. 6.9 +/- 1.4 ml O2*min-1*100 g-1). Local infusion of isoproterenol reversed the delay in regional shortening from 73 +/- 7 to 21 +/- 8 ms, thereby augmenting systolic work (298%) more than positive work (60%), without a significant increase in MVO2 (7.3 +/- 1.5 to 10.5 +/- 3.2 ml O2*min-1*100 g-1). It is concluded that myocardial stunning decreases regional systolic work due to regional mechanical asynchrony, while MVO2 is used supported total positive work which was not significantly reduced. Isoproterenol restores regional work by restoring synchrony, without greatly affecting regional MVO2.